In Sigmadon hispidus cotton rats types 2 and 5 adenoviruses produce diffuse pneumonia consisting of peribronchiolar and alveolar septal monocytic infiltration. Detailed studies with type 5 adenovirus show that the extent of pneumonia and degree of viral replication is strictly dose dependent. Utilizing type 5 ts mutants unable to replicate viral DNA at the non-permissive it was shown that only early viral events are essential to effect the pneumonic infiltrations. Ela deletion mutants did not cause the pneumonic infiltrations, but the block in transcriptions from all other early regions made interpretation of this finding difficult. However, E1b mutants that produce a truncated 55K protein replicate like wild-type (Wt) virus but cause very minimal pneumonia. Deletion of the 5' half of the E3 region, which encodes a 19K glycoprotein, produces more extensive pneumonia than WT virus. The mechanism(s) producing this increase may require products of more than a single open reading frame (ORF) in E3. The pathology and replication of wild-type and vaccine strains of type 4 adenovirus are being studied following intranasal inoculation or oral ingestion.